HIV disease is a continuum of progressive damage to the immune system from the time of infection to the manifestation of severe immunologic damage by opportunistic infections, neoplasms, wasting, or low CD4 lymphocyte count, that define AIDS. In the absence of antiretroviral therapy, this results in an important immunologic impairment with the consequent appearance of opportunistic infections and, lastly, death. The time it takes to traverse this spectrum varies greatly, ranging from 1 year or less in some persons to a still unknown upper limit in others that has reached neatly 20 years in a few individuals.
Significant advances in antiretroviral therapy of HIV infection have been made since the introduction of zidovudine (AZT) in 1987. Intensive research on HIV led to the development of highly active antiretroviral therapies (HAART). HAART is defined as treatment with at least three active anti-retroviral medications, commonly reverse transcriptase inhibitors and protease inhibitors. These therapies have been extremely successful in controlling the spread of the disease. Indeed, with the advent of HAART, HIV infection is now manageable as a chronic disease in patients who have access to medication and who achieve durable virological suppression.
However, residual chronic inflammation persists in HAART-treated patients and is associated with increased risk of cardiovascular diseases and mortality. Both AIDS and non-AIDS mortality are attributed to chronic inflammation in HIV-infected individuals. No therapeutic strategy exists to reduce this inflammation efficiently. This is in part explained by the fact that the inflammatory pathways involved are not well identified. Chronic immune activation is considered as the major driving force for CD4+ T cell depletion and progression towards AIDS in HIV-infected individuals. HIV-triggered chronic inflammation remains higher even in patients who control viral load (patients under efficient anti-retroviral treatment and HIV controllers in companion to healthy donors. Current antiretroviral treatments are highly efficient, but fail to abolish residual chronic immune activation.
There is thus an urgent to understand the factors, which drive this inflammation and to define good surrogate markers for this inflammation.